The main objectives of this proposal are threefold: 1) the evaluation of the anti-tumor effects of membrane sugar-analogs, 2) characterization of the inhibitory activity of nucleotide and nucleotide-sugar analogs on sialyltransferase activity which is elevated in the sera of cancer patients and 3) characterization of surface enzymes in metastasizing tumor cells and an assessment of anti-metastasizing capabilities of agents which modify the cell surface. 6-F-Galactose and 6-F-fucose have been shown to be incorporated into cellular glycoconjugate. These agents are relatively non-toxic in vitro and in vivo but they do modify membrane biochemistry. We now plan to assess the ability of these compounds to limit or decrease tumor spread via metastasis. Another program underway in the laboratory is the assessment of the chemotherapeutic potential of combinations of sugar with nucleoside analogs. The combination of 6-azaribine with glucosamine has resulted in a dramatic lowering of intracellular UTP and CTP pools in L-1210 cells resulting in significantly increased toxicity over each compound administered alone. Combinations such as this are now being tested in vivo in hopes of also obtaining synergistic effects. Metabolic studies of labeled sugar analogs are also being pursued along with a thorough examination of the effects of these analogs on membrane protein and glycoprotein biosynthesis. It is expected that these investigations will result in the development of new agents or combination of agents which may specifically interfere with the metabolism or function of tumor cell plasma membrane glycoconjugate and thereby inhibit tumor growth and/or metastasis.